Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine
Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine
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预暴露于吗啡或安非他明后介导运动敏化长期表达的多巴胺能机制
作者：
L. Vanderschuren;A. Schoffelmeer;A. H. Mulder;T. Vries
摘要研究了多巴胺能机制在阿片类和精神兴奋剂诱导的长期运动敏化中的作用。为此，大鼠行为致敏与吗啡或安非他明和3周后停止治疗挑战各种直接和间接的多巴胺受体激动剂。吗啡和安非他明预处理的大鼠表现出安非他明，可卡因和选择性多巴胺再摄取抑制剂GBR-12909的运动效应的敏化。多巴胺D2/D3受体激动剂quinpirole的运动刺激作用的致敏观察安非他明，但不是吗啡预处理的大鼠。相比之下，吗啡，但不是安非他明预处理的大鼠出现低敏感的运动抑制作用，推测D2-自身受体选择性，剂量的quinpirole。无论是预处理诱导致敏多巴胺D1/D2激动剂阿扑吗啡或多巴胺D1激动剂SKF-82958。事实上，SKF-82958的运动刺激作用在预先暴露于安非他明的动物中似乎有所降低。这些结果表明，突触前多巴胺释放机制的功能变化代表了吗啡和安非他明诱导的运动敏化的长期表达中涉及的常见神经适应。突触前多巴胺D2和突触后D2和/或D3受体差异参与吗啡和安非他明诱导的运动敏化的表达。在一项平行研究中，我们报告说，所有的药物，引起致敏的运动反应，吗啡或安非他明预处理的大鼠引起恢复先前熄灭的海洛因或可卡因寻求行为，分别。总之，这些数据表明，寻求毒品的行为和药物致敏之间存在着明显的关系。
Abstract The role of dopaminergic mechanisms in opiate- and psychostimulant-induced long-term locomotor sensitization was investigated. To that aim, rats were behaviourally sensitized with morphine or amphetamine and 3 weeks after cessation of treatment challenged with various direct and indirect dopamine agonists. Both morphine- and amphetamine-pretreated rats displayed sensitization of the locomotor effects of amphetamine, cocaine, and the selective dopamine reuptake inhibitor GBR-12909. Sensitization of the locomotor stimulant effects of the dopamine D2/D3 receptor agonist quinpirole was observed in amphetamine- but not morphine-pretreated rats. In contrast, morphine-, but not amphetamine-pretreated rats appeared hyposensitive to the locomotor inhibitory effects of a low, presumably D2-autoreceptor selective, dose of quinpirole. Neither pretreatment induced sensitization to the dopamine D1/D2 agonist apomorphine or the dopamine D1 agonist SKF-82958. In fact, the locomotor stimulant effects of SKF-82958 appeared to be decreased in animals pre-exposed to amphetamine. These results suggest that functional changes in presynaptic dopamine release mechanisms represent common neuroadaptations involved in the long-term expression of morphine- and amphetamine-induced locomotor sensitization. Presynaptic dopamine D2 and postsynaptic D2 and/or D3 receptors are differentially involved in the expression of morphine- and amphetamine-induced locomotor sensitization. In a parallel study, we report that all of the drugs that elicited sensitized locomotor responses in morphine- or amphetamine-pretreated rats caused reinstatement of previously extinguished heroin- or cocaine-seeking behaviour, respectively. Taken together, these data suggest a marked relationship between drug-seeking behaviour and drug sensitization.
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DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
M. Wolf;F. J. White;R. Nassar;R. J. Brooderson;M. Khansa
通讯作者：
M. Wolf;F. J. White;R. Nassar;R. J. Brooderson;M. Khansa
戒断连续或间歇性可卡因给药：D2 受体功能的变化。
DOI：
--
发表时间：
1994
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
King,GR;EllinwoodJr,EH;Silvia,C;Joyner,CM;Xue,Z;Caron,MG;Lee,TH
通讯作者：
Lee,TH
安非他明在重复给予可卡因的大鼠中优先在伏核壳中产生运动敏化和细胞外多巴胺。
DOI：
--
发表时间：
1995
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Pierce,RC;Kalivas,PW
通讯作者：
Kalivas,PW
重复给予安非他明会改变大鼠纹状体中 D1 刺激的腺苷酸环化酶活性与钙调蛋白之间的相互作用。
DOI：
--
发表时间：
1990
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Roseboom,PH;Hewlett,GH;Gnegy,ME
通讯作者：
Gnegy,ME
影响因子：
56.9
作者：
GREENGARD, P;VALTORTA, F;BENFENATI, F
通讯作者：
BENFENATI, F